A paracrine requirement for hedgehog signalling in cancer

被引：798

作者：

Yauch, Robert L. ^{[1
]}

Gould, Stephen E. ^{[1
]}

Scales, Suzie J. ^{[1
]}

Tang, Tracy ^{[1
]}

Tian, Hua ^{[1
]}

Ahn, Christina P. ^{[1
]}

Marshall, Derek ^{[1
]}

Fu, Ling ^{[1
]}

Januario, Thomas ^{[1
]}

Kallop, Dara ^{[1
]}

Nannini-Pepe, Michelle ^{[1
]}

Kotkow, Karen ^{[2
]}

Marsters, James C., Jr. ^{[1
]}

Rubin, Lee L. ^{[2
]}

de Sauvage, Frederic J. ^{[1
]}

机构：

[1] Genentech Inc, San Francisco, CA 94080 USA

[2] Curis Inc, Cambridge, MA 02138 USA

来源：

NATURE | 2008年 / 455卷 / 7211期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/nature07275

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Ligand- dependent activation of the hedgehog (Hh) signalling pathway has been associated with tumorigenesis in a number of human tissues(1-7). Here we show that, although previous reports have described a cell- autonomous role for Hh signalling in these tumours(1-7), Hh ligands fail to activate signalling in tumour epithelial cells. In contrast, our data support ligand- dependent activation of the Hh pathway in the stromal microenvironment. Specific inhibition of Hh signalling using small molecule inhibitors, a neutralizing anti- Hh antibody or genetic deletion of smoothened ( Smo) in the mouse stroma results in growth inhibition in xenograft tumour models. Taken together, these studies demonstrate a paracrine requirement for Hh ligand signalling in the tumorigenesis of Hh- expressing cancers and have important implications for the development of Hh pathway antagonists in cancer.

引用

页码：406 / U61

页数：6

共 30 条

[1] Tissue repair and stem cell renewal in carcinogenesis [J].